Abstract 5384: Acute Lipid Infusion Causes Macrophage Infiltration, Local Inflammation, and Suppresses AMPK in Heart

Abstract

Obesity and hyperlipidemia are major risk factors of heart disease. Recent studies showed that inflammation is associated with obesity and plays a role in the pathogenesis of diabetic complications. In this report, we examined the effects of lipid on cardiac inflammation and metabolism. Intralipid (2.5 ml/kg/hr; triglyceride emulsion) and heparin (6 U/hr) or glycerol (control) were intravenously infused for 5 hrs to raise circulating fatty acids (FFA) levels in awake C57BL/6 mice (n=10~11). Plasma FFA levels were raised by 3.5-fold over the glycerol-infused groups, and heart samples were taken at the end of experiments. Acute lipid infusion caused cardiac inflammation and increased local macrophage-specific CD68 levels in heart (Fig. 1 ; * P <0.05). Local levels of cytokines (IL-6 and TNF-α) were elevated by ~2-fold following lipid infusion (Fig. 2 ). Heart expression of the C-C motif chemokine receptor-2 (CCR2), which binds the MCP-1 was elevated by 70% following lipid infusion, and this was associated with increased levels of MyD88 in heart, supporting the role of TLR4 signaling in lipid-induced cardiac inflammation. Lipid-induced elevation of local cytokine levels resulted in increased cardiomyocyte expression of SOCS3 (Fig. 3 ). Further, acute lipid infusion reduced total AMPK protein levels and Thr 172 phosphorylation of AMPK in heart (Fig. 4 ). These data are consistent with the role of inflammation in the regulation of myocardial AMPK. Our findings indicate that fatty acids and nutrient stress are involved in obesity-induced cardiac inflammation and alterations in myocardial glucose metabolism.